Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells
2008

Chemical-Genetic Profiling of Imidazo Compounds Reveals Target Pathways in Yeast and Human Cells

publication 10 minutes Evidence: high

Author Information

Author(s): Yu Lisa, Lopez Andres, Anaflous Abderrahmane, El Bali Brahim, Hamal Abdellah, Ericson Elke, Heisler Lawrence E., McQuibban Angus, Giaever Guri, Nislow Corey, Boone Charles, Brown Grant W., Bellaoui Mohammed

Primary Institution: University of Toronto

Hypothesis

How do imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines affect cellular processes in yeast and human cells?

Conclusion

The study found that imidazo[1,2-a]pyridines disrupt mitochondrial function while imidazo[1,2-a]pyrimidines cause nuclear DNA damage.

Supporting Evidence

  • Compound 13 was found to disrupt mitochondrial function.
  • Compound 15 caused nuclear DNA damage and induced mutagenesis.
  • Chemical-genetic profiles in yeast can predict the mode of action in mammalian cells.
  • Different chemical structures of compounds lead to different biological effects.
  • Both compounds were toxic to human cells, but with different potencies.

Takeaway

This study shows that two similar compounds can affect cells in very different ways: one harms mitochondria and the other damages DNA.

Methodology

The study used chemical-genetic profiling in yeast to analyze the effects of imidazo compounds on cellular processes.

Statistical Information

P-Value

2.33×10−36

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pgen.1000284

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